Clinicopathologic Features of Anal and Perianal Squamous Cell Carcinomas and Their Relationship to Human Papillomavirus

Abstract

Anal squamous cell carcinomas (ASCCs) frequently harbor human papillomavirus (HPV), most commonly high-risk (HR-) HPV type 16. While p16 immunohistochemistry (IHC) is typically used as a surrogate for HR-HPV status in the oropharynx and cervix, its overexpression can also occur as a result of oncogenic stress and sometimes prove nonspecific. There have been recent investigations into the use of HPV RNA in situ hybridization (RISH) assays as an alternative method, which have shown robust results for squamous cell carcinomas of the oropharynx and cervix. Our study evaluated HPV RISH and p16 IHC in 50 ASCCs, as well as the clinicopathologic features of ASCC relative to HPV status. We found that HPV RISH and p16 IHC were closely in agreement with 96% concordance. Using the 2 methodologies, 78% of ASCCs were HR-HPV positive, 10% were low-risk HPV positive, and 12% were HPV-negative. None of our cases showed co-infection across HR-HPV and low-risk HPV. ASCCs that were not related to HR-HPV were more likely to have a typical keratinizing morphology (P=0.05) and more likely to involve the perianal area (P=0.006). HPV-negative cases were particularly aggressive with high rates of metastases and patient death within 2 years of diagnosis. Overall, HPV RISH appears to be a reliable methodology for testing, and HPV status may have implications for prognostication of ASCCs.

Diagnostic Usefulness of p16 Immunohistochemistry for some Epithelial Lesions in the Pathology Service of Sultan Qaboos University Hospital

“…On the other hand, labial squamous cell carcinoma was negative (14). Moreover, it was used in anal intraepithelial and anal squamous cell carcinoma, where both of them were positive, in concordance with previous works (15,16). Furthermore, our results showed that it can be applied in patients with oropharyngeal squamous cell carcinoma, where its cellular expression was predominantly patchy to negative stain, indicating that these lesions where mostly HPV independent (17).…”

CYLD-mutant cylindroma-like basaloid carcinoma of the anus: a genetically and morphologically distinct class of HPV-related anal carcinoma

“…Most cancers of the anal and perianal region are squamous cell carcinomas (SCC), predominantly HPV-related [1][2][3][4]. Previous publications have reported rare occurrences of anal carcinomas (AC) with "adenoid cystic carcinoma-like" or "cylindroma-like" histologic features, including dense hyaline inclusions of basement membrane material within tumor lobules resembling cutaneous cylindroma [5][6][7].…”

Prognostic and predictive role of YKL-40 in anal squamous cell carcinoma: a serological and tissue-based analysis in a multicentric cohort

“…It is well-known that ASC is related to HPV infection ( 4 , 5 ). Thus, to further evaluate the adequacy of our cohort, we assessed the protein expression of p16 INK4a (p16) in the primary lesions as a surrogate of HPV infection status ( 53 – 57 ). The p16 IHC stain was available for assessment in 67 cases, and most cases (92.5%, 62/67) were positive.…”